Abstract | BACKGROUND: RNA interference has received much attention as a novel therapeutic strategy. MicroRNA ( miRNA) appears to be promising as a novel nucleic-acid medicine because it is able to suppress a series of protein expression that relates to a specific event such as angiogenesis. In the present study, we used dicetyl phosphate- tetraethylenepentamine-based polycation liposomes ( TEPA-PCL) as a delivery system for miR-92a, one of the miRNAs regulating angiogenesis, and attempted to deliver miR-92a to angiogenic endothelial cells for the development of cancer therapy by anti-angiogenesis. METHODS: RESULTS: The complex of miR-92a-C with TEPA-PCL was formed and miR-92a-C remained stable with TEPA-PCL at the N/P ratio of 10. After transfection of HUVECs with miR-92a-C complex, miR-92a-C spread into the whole cytoplasm of the cells without any change of cellular morphology, and the expression of several proteins encoded by miR-92a-target genes was suppressed. Furthermore, the capability of forming capillary tubes was impaired in complex-treated HUVECs. CONCLUSIONS: We have developed a miR-92a delivery system into angiogenic endothelial cells by the use of TEPA-PCL. These results suggest that miR-92a-C/ TEPA-PCL is promising for the treatment of tumors via the suppression of angiogenesis.
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Authors | Hidenori Ando, Ayaka Okamoto, Masafumi Yokota, Kosuke Shimizu, Tomohiro Asai, Takehisa Dewa, Naoto Oku |
Journal | The journal of gene medicine
(J Gene Med)
Vol. 15
Issue 1
Pg. 20-7
(Jan 2013)
ISSN: 1521-2254 [Electronic] England |
PMID | 23239404
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 John Wiley & Sons, Ltd. |
Chemical References |
- Angiogenesis Inhibitors
- Ethylenediamines
- Integrin alpha5
- Liposomes
- MIRN92 microRNA, human
- MicroRNAs
- Receptors, Lysosphingolipid
- S1PR1 protein, human
- Sphingosine-1-Phosphate Receptors
- MAP Kinase Kinase 4
- tetraethylenepentamine
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Topics |
- Angiogenesis Inhibitors
(metabolism)
- Blotting, Western
- Cells, Cultured
- Ethylenediamines
(pharmacology)
- Gene Expression Regulation
- Gene Knockdown Techniques
- Gene Transfer Techniques
- Human Umbilical Vein Endothelial Cells
- Humans
- Integrin alpha5
(genetics, metabolism)
- Liposomes
- MAP Kinase Kinase 4
(genetics, metabolism)
- MicroRNAs
(genetics, metabolism)
- Microscopy, Confocal
- Neoplasms
(therapy)
- Neovascularization, Pathologic
(therapy)
- RNA Interference
- Receptors, Lysosphingolipid
(genetics, metabolism)
- Sphingosine-1-Phosphate Receptors
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